Genetic evaluation of patients with multiple primary cancers.

Regarding inherited cancer predisposition, single gene carriers of pathogenic variants (PVs) have been extensively reported on in the literature, whereas the oligogenic coinheritance of heterozygous PVs in cancer-related genes is a poorly studied event. Currently, due to the increased number of cancer survivors, the probability of patients presenting with multiple primary cancers (MPCs) is higher. The present study included patients with MPCs aged ≤45 years without known PVs in common cancer predisposition genes. This study used whole exome sequencing (WES) of germline and tumoral DNA, chromosomal microarray analysis (CMA) of germline DNA (patients 1-7, 9 and 10), and a karyotype test of patient 8 to detect variants associated with the disease. The 10 patients included in the study presented a mean of 3 cancers per patient. CMA showed two microduplications and one microdeletion, while WES of the germline DNA identified 1-3 single nucleotide variants of potential interest to the disease in each patient and two additional copy number variants. Most of the identified variants were classified as variants of uncertain significance. The mapping of the germline variants into their pathways showed a possible additive effect of these as the cause of the cancer. A total of 12 somatic samples from 5 patients were available for sequencing. All of the germline variants were also present in the somatic samples, while no second hits were identified in the same genes. The sequencing of patients with early cancers, family history and multiple tumors is already a standard of care. However, growing evidence has suggested that the assessment of patients should not stop at the identification of one PV in a cancer predisposition gene.

Natural history of salivary gland secretory carcinoma: A REFCOR study.

BACKGROUND AND OBJECTIVES: Salivary gland Secretory Carcinoma (SC), characterized by Skalova in 2010 is a rare tumor studied within the REFCOR (French Network of experts on Rare Head and Neck Cancers). We conducted a prospective multicentric cohort study of 108 SC cases in the REFCOR database up to July 2021, analyzing diagnostic, therapeutic, and survival data. METHODS: Data was collected prospectively from diagnosis to the last update. Each patient had two histological readings including one by a REFCORpath pathologist, and all cases underwent molecular testing to confirm diagnosis. Statistical analyses were performed using R software. RESULTS: MRI was not contributive to malignancy diagnosis. After 2 histological readings, 79 % of patients were diagnosed, with 21 % requiring molecular testing to confirm diagnosis. Surgical treatment typically involved tumor excision and lymph node dissection. The tumor exhibited low lymph node involvement, with 95 % of patients being cN0, and no nodal metastases post-dissection. Five-year overall survival and recurrence-free survival were 91.4 % {95 % CI (0.84-1)} and 89 % {95 % CI (0.81; 0.98)} respectively, indicating a favorable prognosis. CONCLUSIONS: SC is a rare and newly recognized tumor, with generally favorable outcomes. Our cohort, among the largest to date, provides valuable insights. Future research should refine treatment guidelines.

Biobanking rare gynaecological tumours - How harmonised is data collection?

INTRODUCTION: GYNOCARE, the European Network for Gynaecological Rare Cancer Research, set out to evaluate the current status of biobanks with access to rare gynaecological tumours, with a view to harmonising sample and data collection and associated consent, to facilitate collaborative cross-border research, enabling clinical trials and translational research. METHODS: Two digital surveys were formulated, one covering clinical and scientific parameters and one exploring ethical and regulatory issues around informed consent. RESULTS: Data were analysed for 20 common responses, from 7 European countries. Tissue was the main sample type biobanked with 63 % also banking blood. Documentation of clinical data, treatment regimens and classification systems varied. Eighty percent collected pathological information. Most biobanks were linked to medical records but only one fifth with national registries. The Information Sheet covered governance, benefits/risks, sharing (mainly for non-profit research), return of results and data protection safeguards. Only 37 % informed patients about sample and data storage, although about half stored samples for an indefinite time. Pseudonymisation and Data Protection Officer approval were the prime data safeguards. Less than half explained the difference between anonymisation and pseudonymisation. Broad consent was the norm (84 %) and 95 % granted the right to withdraw consent. Three countries have Biobank legislation. CONCLUSION: These surveys provide a snapshot of the current state of biobanks and highlight divergences in the consent process and data management. More work is needed to understand what parameters are being gathered across more EU countries and thus harmonise the sample and data collection processes to facilitate cross-border research.

Enhanced Detection of Gastrointestinal Malignancies using Machine Learning-Optimized Liquid Biopsy: A Mini Review.

BACKGROUND: Gastrointestinal (GI) cancers represent some of the most common and lethal malignancies globally, underscoring the urgent need for improved diagnostic strategies. Traditional diagnostic methods, while effective to some degree, are often invasive and unsuit-able for regular screenings. OBJECTIVE: This review article explores integrating machine learning (ML) with liquid biopsy techniques as a revolutionary approach to enhance the detection and monitoring of GI cancers. Liquid biopsies offer a non-invasive alternative for cancer detection through the analysis of circulating tumor DNA (ctDNA) and other biomarkers, which when combined with ML, can significantly improve diagnostic accuracy and patient outcomes. METHODS: We conducted a comprehensive review of recent advancements in liquid biopsy and ML, focusing on their synergistic potential in the early detection of GI cancers. The review addresses the application of next-generation sequencing and digital droplet PCR in enhancing the sensitivity and specificity of liquid biopsies. RESULTS: Machine learning algorithms have demonstrated remarkable ability in navigating complex datasets and identifying diagnostically significant patterns in ctDNA and other circu-lating biomarkers. Innovations such as machine learning-enhanced "fragmentomics" and tomographic phase imaging flow cytometry illustrate significant strides in non-invasive cancer diagnostics, offering enhanced detection capabilities with high accuracy. CONCLUSION: The integration of ML in liquid biopsy represents a transformative step in the early detection and personalized treatment of GI cancers. Future research should focus on overcoming current limitations, such as the heterogeneity of tumor-derived genetic materials and the standardization of liquid biopsy protocols, to fully realize the potential of this technol-ogy in clinical settings.

Comprehensive structure-function analysis reveals gain- and loss-of-function mechanisms impacting oncogenic KRAS activity.

To dissect variant-function relationships in the KRAS oncoprotein, we performed deep mutational scanning (DMS) screens for both wild-type and KRASG12D mutant alleles. We defined the spectrum of oncogenic potential for nearly all possible KRAS variants, identifying several novel transforming alleles and elucidating a model to describe the frequency of KRAS mutations in human cancer as a function of transforming potential, mutational probability, and tissue-specific mutational signatures. Biochemical and structural analyses of variants identified in a KRASG12D second-site suppressor DMS screen revealed that attenuation of oncogenic KRAS can be mediated by protein instability and conformational rigidity, resulting in reduced binding affinity to effector proteins, such as RAF and PI3-kinases, or reduced SOS-mediated nucleotide exchange activity. These studies define the landscape of single amino acid alterations that modulate the function of KRAS, providing a resource for the clinical interpretation of KRAS variants and elucidating mechanisms of oncogenic KRAS inactivation for therapeutic exploitation.

Managements for perioperative anxiety in patients with gastrointestinal cancers.

Gastrointestinal (GI) cancers are the most common malignancies, while surgical intervention remains the sole therapeutic approach offering the possibility of a definite cure for cancer. Perioperative anxiety negatively impacts the recovery of GI cancers. Recently, mounting studies have demonstrated that proper nursing interventions may alleviative perioperative anxious illnesses in patients with GI cancers. We conducted a first comprehensive review to summarize all the current evidence on this topic. After a systematically search in the six common databases, eighteen relevant studies were included for further analysis. The present review highlighted that there is a high prevalence of perioperative anxiety in patients with GI cancers (e.g., colorectal cancer, gastric/stomach cancer, hepatocellular carcinoma, gallbladder cancer, and esophageal cancer), while specific nursing interventions are the reliable methods to reduce postoperative anxiety. These nursing strategies include, but are not limited to, therapeutic listening intervention, implementing perioperative music, predictive nursing, progressive relaxation exercises, psychological interventions in the nursing care, comprehensive nursing, continuous nursing care, video-based nursing education, multidisciplinary cooperative continuous care, accelerated rehabilitation nursing, TCM nursing, evidence-based early warning nursing, target nursing care, and high-quality nursing. Since several limitations existed in the eligible studies as well as in this review, a well-designed multicenter RCT with large sample size is still warranted for the confirmation of nursing intervention for managing perioperative anxiety in patients with GI cancers. Also, future studies should focus on the long-term effects of relevant interventions, specific patient populations, multidisciplinary approaches, technological innovations, and educational programs.

Simultaneous robotic hemicolectomy and robotic partial nephrectomy via a posterior approach.

Introduction: Advances in diagnostic technologies have resulted in an increase in patients with synchronous cancers. We report robotic hemicolectomy and robotic partial nephrectomy via a posterior approach. Case presentation: A 72-year-old woman presented with synchronous ascending colon and right kidney cancers. We performed simultaneous robotic right hemicolectomy and robotic right partial nephrectomy. The renal tumor was located in a posterior and mid-lower pole of the kidney, we positioned the ports similar to the retroperitoneal approach and to gain a confronting approach to the tumor. Conclusion: Considering preoperative evaluations and intraoperative conditions comprehensively, it is essential to flexibly adapt to the appropriate surgical position and port arrangement to perform the surgery with consideration for oncological principles.

Histoplasmosis in cancer patients: A global scoping review (2001-2024).

Although classified as an AIDS-defining illness, several reports show histoplasmosis also affects patients living with cancers including haematological malignancies and solid tumours. However, reviews describing cases of histoplasmosis in malignancies are lacking in the literature. We identified a total of thirty-four cases with twenty (58.8 %) cases reported from the USA, four from Brazil (11.8 %), three from India (8.8 %), and one each from Singapore (2.9 %), France (2.9 %), Netherlands (2.9 %), Colombia (2.9 %), Canada (2.9 %), Morocco (2.9 %), and Malaysia (2.9 %). 82.4 % (n = 28) of the cases were adults. Presenting symptoms were majorly fever (61.7 %), lymphadenopathy (50.0 %) and weight loss (29.4 %). Essential haematologic findings were pancytopaenia (n = 7, 20.6 %), neutropenia (n = 2, 5.9 %) and anaemia (n = 5, 14.7 %). The associated cancers were predominantly haematological and comprised 73.5 % (n = 25) of all cases. The diagnosis of histoplasmosis was via histopathology (n = 23, 67.6%), culture (n = 13, 38.2%), Histoplasma antigen assay (n = 13, 38.2%), anti-Histoplasma antibody assay (n = 5, 14.7%), PCR and sequencing (n = 2, 5.9%), peripheral blood film/direct microscopy (n = 4, 11.8%) and cytology (n = 1, 2.9%). Of the thirty-four cases, twenty-four (70.6%) had favourable outcomes, eight (23.5%) died, one (2.9%) was lost to follow-up and in one (2.9%) case, the outcome was not stated. Histoplasmosis is not an uncommon opportunistic disease complicating malignancies but is paradoxically underdiagnosed in Africa given the huge burden of cancers in that region. Besides following chemotherapy and the use of steroids, tumour necrosis factor-α antagonists therapy, hematopoietic stem cell transplantation and environmental exposure were factors associated with Histoplasma infection in patients with malignancies. A resolution to promptly screen suspected or confirmed cases of malignancies for histoplasmosis will improve diagnosis and clinical outcomes.

Clinical commissioning and introduction of an in-house artificial intelligence (AI) platform for automated head and neck intensity modulated radiation therapy (IMRT) treatment planning.

BACKGROUND AND PURPOSE: To describe the clinical commissioning of an in-house artificial intelligence (AI) treatment planning platform for head-and-neck (HN) Intensity Modulated Radiation Therapy (IMRT). MATERIALS AND METHODS: The AI planning platform has three components: (1) a graphical user interface (GUI) is built within the framework of a commercial treatment planning system (TPS). The GUI allows AI models to run remotely on a designated workstation configured with GPU acceleration. (2) A template plan is automatically prepared involving both clinical and AI considerations, which include contour evaluation, isocenter placement, and beam/collimator jaw placement. (3) A well-orchestrated suite of AI models predicts optimal fluence maps, which are imported into TPS for dose calculation followed by an optional automatic fine-tuning. Six AI models provide flexible tradeoffs in parotid sparing and Planning Target Volume (PTV)-organ-at-risk (OAR) preferences. Planners could examine the plan dose distribution and make further modifications as clinically needed. The performance of the AI plans was compared to the corresponding clinical plans. RESULTS: The average plan generation time including manual operations was 10-15  min per case, with each AI model prediction taking ∼1 s. The six AI plans form a wide range of tradeoff choices between left and right parotids and between PTV and OARs compared with corresponding clinical plans, which correctly reflected their tradeoff designs. CONCLUSION: The in-house AI IMRT treatment planning platform was developed and is available for clinical use at our institution. The process demonstrates outstanding performance and robustness of the AI platform and provides sufficient validation.

Médecine nucléaire et cancers de la thyroïde en 2024 : iode 131, TEP et nouvelles approches théranostiques.

NUCLEAR MEDICINE AND THYROID CANCERS IN 2024: IODINE 131, PET AND NEW THERANOSTIC APPROACHES: Nuclear medicine has long been a mainstay in the management of thyroid cancers. In patients with differentiated thyroid cancer (DTC), the most common histotype, radioiodine (RAI, 131I) has been for years a cornerstone for the treatment of RAI-avid metastases. Post-therapeutic 131I scintigraphy helps guide these treatments and contributes to the definition of refractory cancers. In these refractory patients, who represent fewer than 5% of CTDs, 18FDG PET plays a central diagnostic and prognostic role. From a therapeutic perspective, RAI uptake can be re-induced in some of these patients with the BRAF mutation by using redifferentiation protocols. In anaplastic thyroid cancer (A TC) that is rare, aggressive and undifferentiated, 18FDG PET remains the metabolic imaging of choice. In medullary thyroid cancer (MTC), PET imaging is mainly based on the use of 18F-DOPA, even if 18FDG also provides prognostic data and 68Ga-DOTATOC could allow a theranostic approach. Other radiopharmaceuticals offering new theranostic avenues in thyroid cancers are also discussed, such as prostate-specific membrane antigen (PSMA) and fibroblast activation protein (FAP). After decades of a "one-size fits all" approach in thyroid cancer management, molecular imaging is paving the way towards personalized medicine.

Dependence of NPPS creates a targetable vulnerability in RAS-mutant cancers.

RAS is the most frequently mutated oncoprotein for cancer driving. Understanding of RAS biology and discovery of druggable lynchpins in RAS pathway is a prerequisite for targeted therapy of RAS-mutant cancers. The recent identification of KRASG12C inhibitor breaks the "undruggable" curse on RAS and has changed the therapy paradigm of KRAS-mutant cancers. However, KRAS mutations, let alone KRASG12C mutation, account for only part of RAS-mutated cancers. Targeted therapies for cancers harboring other RAS mutations remain the urgent need. In this study we explored the pivotal regulatory molecules that allow for broad inhibition of RAS mutants. By comparing the expression levels of nucleotide pyrophosphatase (NPPS) in a panel of cell lines and the functional consequence of increased NPPS expression in RAS-mutant cells, we demonstrated that cancer cells with various kinds of RAS mutations depended on NPPS for growth and survival, and that this dependence conferred a vulnerability of RAS-mutant cancer to treatment of NPPS inhibition. RAS-mutant cells, compared with RAS-wildtype cells, bored and required an upregulation of NPPS. Transcriptomics and metabolomics analyses revealed a NPPS-dependent hyperglycolysis in RAS-mutant cells. We demonstrated that NPPS promoted glucose-derived glycolytic intermediates in RAS-mutant cells by enhancing its interaction with hexokinase 1 (HK1), the enzyme catalyzing the first committed step of glycolysis. Pharmacological inhibition of NPPS-HK1 axis using NPPS inhibitor Enpp-1-IN-1 or HK1 inhibitor 2-deoxyglucose (2-DG), or genetic interfere with NPPS suppressed RAS-mutant cancers in vitro and in vivo. In conclusion, this study reveals an unrecognized mechanism and druggable lynchpin for modulation of pan-mutant-RAS pathway, proposing a new potential therapeutic approach for treating RAS-mutant cancers.

Healthcare disparities in access to surgical management and outcomes of patients with nonmetastatic primary liver cancer: A population based study from Louisiana tumor registry.

BACKGROUND: This study aims to identify factors associated with disparities in receipt and outcomes of surgical interventions in patients with primary nonmetastatic liver cancers. METHODS: Cases from 2010 to 2020 were identified using Louisiana Tumor Registry. Four surgical categories were utilized: none, ablation, resection, transplant. Bivariate relationships were assessed via Chi-square tests. Overall survival (OS) was visualized using Kaplan Meier plots, compared via log-rank test, and analyzed with Cox proportional hazards models. RESULTS: Only 24.5 â€‹% of patients underwent surgical interventions. Black race had decreased odds of undergoing transplant and decreased OS with transplant. Uninsured, Medicaid, and rural residence had decreased odds of receiving surgical intervention. Older age and no domestic partner had decreased odds of transplant. Older age, male sex, no domestic partner, and rural residence had decreased OS post-transplant. CONCLUSIONS: Identifying the population at risk for not receiving surgical intervention and allocating resources to access care is crucial to improve outcomes.

A review on optimization of Wilms tumour management using radiomics.

Background: Wilms tumour, a common paediatric cancer, is difficult to treat in low- and middle-income countries due to limited access to imaging. Artificial intelligence (AI) has been introduced for staging, detecting, and classifying tumours, aiding physicians in decision-making. However, challenges include algorithm accuracy, translation into conventional diagnosis, reproducibility, and reliability. As AI technology advances, radiomics, an AI tool, emerges to extract tumour morphology and stage information. Objectives: This review explores the application of radiomics in Wilms tumour management, including its potential in diagnosis, prognosis, and treatment. Additionally, it discusses the future prospects of AI in this field and potential directions for automation-aided Wilms tumour treatment. Methods: The review analyses various research studies and articles on the use of radiomics in Wilms tumour management. This includes studies on automated deep learning-based classification, interobserver variability in histopathological analysis, and the application of AI in staging, detecting, and classifying Wilms tumours. Results: The review finds that radiomics offers several promising applications in Wilms tumour management, including improved diagnosis: it helps in classifying Wilms tumours from other paediatric kidney tumours, prognosis prediction: radiomic features can be used to predict both staging and response to preoperative chemotherapy, Treatment response assessment: Radiomics can be used to monitor the response of Wilms and to predict the feasibility of nephron-sparing surgery. Conclusions: This review concludes that radiomics has the potential to significantly improve the diagnosis, prognosis, and treatment of Wilms tumours. Despite some challenges, such as the need for further research and validation, AI integration in Wilms tumour management offers promising opportunities for improved patient care. Advances in knowledge: This review provides a comprehensive overview of the potential applications of radiomics in Wilms tumour management and highlights the significant role AI can play in improving patient outcomes. It contributes to the growing body of knowledge on AI-assisted diagnosis and treatment of paediatric cancers.

Non-acquired immunodeficiency syndrome defining malignancies in people living with haemophilia and human immunodeficiency virus after direct-acting antiviral era.

Non-acquired immunodeficiency syndrome-defining malignancies (NADMs) are the crucial cause of mortality in people living with haemophilia and human immunodeficiency virus (PLWHH). We aimed to analyse the types and characters of NADMs in PLWHH after approval of direct-acting antivirals (DAA), considering that most PLWHH are infected with hepatitis C virus (HCV). We conducted a nationwide questionnaire mail survey across 395 HIV core facilities in Japan between May 2022 and February 2023. Eight-year data from 64 respondent hospitals (n = 328 PLWHH; 2015-2022) were collected; 35 NADM cases were identified and analysed. Standardised cancer incidence ratios (SCIRs) were calculated. The median age of PLWHH with NADMs was 51 years (interquartile range: 47-62 years); the SCIR was 2.08 (95% confidence interval [CI]: 1.48-2.90) for all malignancies (including carcinoma in situ). Liver cancer accounted for most NADMs (43% [15/35]). The SCIRs of liver cancer (23.09 [95% CI: 13.92- 38.30]) and papillary thyroid cancer (9.38 [2.35-37.50]) significantly increased after adjusting for general Japanese male sex and age. Among PLWHH with liver cancers, 73% (11/15) achieved HCV-sustained virological response. Notably, for patients aged ≤ 50 years, 47% (7/15) were affected by liver cancers, and 27% (4/15) succumbed to NADMs. This study presents the largest survey of NADMs in PLWHH after DAA approval. Our findings emphasised the elevated risk of malignancies in PLWHH, underscoring the need for early cancer screening and preventive measures, particularly against liver cancers, even in younger PLWHH.

Surgical management of a chest wall osteosarcoma with pleural and lung invasion through en-bloc chest resection and complex reconstruction. Case report.

Osteosarcomas of the ribs are rarely reported but have a high potential for pulmonary metastases. The therapeutic strategies for this disease are not well defined. The primary treatment recommendations include wide resection with clear surgical margins and chest wall reconstruction if needed. We present a case of costal osteosarcoma with pleural and lung extension successfully treated by en-bloc thoracic resection with free surgical margins and chest wall reconstruction with rib titanium bars, polypropylene mesh and a rectus abdominis free flap with microvascular anastomoses. This case demonstrates the importance of this therapeutic strategy and highlights the need of early intervention in managing this disease.

Advances and challenges in the use of liquid biopsy in gynaecological oncology.

Ovarian cancer, endometrial cancer, and cervical cancer are the three primary gynaecological cancers that pose a significant threat to women's health on a global scale. Enhancing global cancer survival rates necessitates advancements in illness detection and monitoring, with the goal of improving early diagnosis and prognostication of disease recurrence. Conventional methods for identifying and tracking malignancies rely primarily on imaging techniques and, when possible, protein biomarkers found in blood, many of which lack specificity. The process of collecting tumour samples necessitates intrusive treatments that are not suitable for specific purposes, such as screening, predicting, or evaluating the effectiveness of treatment, monitoring the presence of remaining illness, and promptly detecting relapse. Advancements in treatment are being made by the detection of genetic abnormalities in tumours, both inherited and acquired. Newly designed therapeutic approaches can specifically address some of these abnormalities. Liquid biopsy is an innovative technique for collecting samples that examine specific cancer components that are discharged into the bloodstream, such as circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), cell-free RNA (cfRNA), tumour-educated platelets (TEPs), and exosomes. Mounting data indicates that liquid biopsy has the potential to improve the clinical management of gynaecological cancers through enhanced early diagnosis, prognosis prediction, recurrence detection, and therapy response monitoring. Understanding the distinct genetic composition of tumours can also inform therapy choices and the identification of suitable targeted treatments. The main benefits of liquid biopsy are its non-invasive characteristics and practicality, enabling the collection of several samples and the continuous monitoring of tumour changes over time. This review aims to provide an overview of the data supporting the therapeutic usefulness of each component of liquid biopsy. Additionally, it will assess the benefits and existing constraints associated with the use of liquid biopsy in the management of gynaecological malignancies. In addition, we emphasise future prospects in light of the existing difficulties and investigate areas where further research is necessary to clarify its rising clinical capabilities.

Research progress of MUC1 in genitourinary cancers.

MUC1 is a highly glycosylated transmembrane protein with a high molecular weight. It plays a role in lubricating and protecting mucosal epithelium, participates in epithelial cell renewal and differentiation, and regulates cell adhesion, signal transduction, and immune response. MUC1 is expressed in both normal and malignant epithelial cells, and plays an important role in the diagnosis, prognosis prediction and clinical monitoring of a variety of tumors and is expected to be a new therapeutic target. This article reviews the structural features, expression regulation mechanism, and research progress of MUC1 in the development of genitourinary cancers and its clinical applications.

High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome.

Aim: Lynch syndrome (LS) is a dominantly inherited syndrome characterized by an increased risk for LS associated tumors such as colorectal cancer (CRC) and gastric cancer (GC). However, the clinical benefit of surveillance for GC remains unclear while it has already been recommended for CRC. This study aimed to elucidate the clinical features of GC in Japanese individuals with LS, and the risk of developing multiple GCs to build regional-tailored surveillance programs in LS patients with GC. Methods: Data on Japanese individuals with LS were retrospectively collected from a single institution. The clinical features of GC, including the cumulative risk of multiple GCs, were analyzed. Results: Among 96 individuals with LS (MLH1/MSH2/MSH6, 75:20:1), 32 GC lesions were detected in 15 individuals with LS (male/female, 11:4). The median age at initial GC diagnosis was 52.7 y (range: 28-71). Histological examination revealed a predominance of intestinal type (19/24: 87.5%). Moreover, the majority of the GC lesions (82%) were determined to have high-frequency of microsatellite instability. The cumulative risk of individuals with LS developing GC at 70 y was 31.3% (MLH1 36.1%, MSH2 18.0%). Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20 y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively. Conclusion: Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC.

Recent advances in and applications of ex vivo drug sensitivity analysis for blood cancers.

Blood cancers, including leukemia, multiple myeloma, and lymphoma, pose significant challenges owing to their heterogeneous nature and the limitations of traditional treatments. Precision medicine has emerged as a transformative approach that offers tailored therapeutic strategies based on individual patient profiles. Ex vivo drug sensitivity analysis is central to this advancement, which enables testing of patient-derived cancer cells against a panel of therapeutic agents to predict clinical responses. This review provides a comprehensive overview of the latest advancements in ex vivo drug sensitivity analyses and their application in blood cancers. We discuss the development of more comprehensive drug response metrics and the evaluation of drug combinations to identify synergistic interactions. Additionally, we present evaluation of the advanced therapeutics such as antibody-drug conjugates using ex vivo assays. This review describes the critical role of ex vivo drug sensitivity analyses in advancing precision medicine by examining technological innovations and clinical applications. Ultimately, these innovations are paving the way for more effective and individualized treatments, improving patient outcomes, and establishing new standards for the management of blood cancers.

NEK2 is a potential pan-cancer biomarker and immunotherapy target.

BACKGROUND: NEK2 is a member of the NEKs family and plays an important role in cell mitosis. Increasing evidence suggests that NEK2 is associated with the development of multiple tumors, but systematic studies of NEK2 in cancer are still lacking. Therefore, we evaluated the prognostic value of NEK2 in 33 cancers to elucidate the potential function of NEK2 in pan-cancers. METHODS: We investigated the role of NEK2 in pan-cancers utilizing The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. Additionally, we analyzed the association between NEK2 gene expression across various cancers, protein expression, the tumor microenvironment (TME), and drug sensitivity using several software and web platforms.The potential oncogenic role of NEK2 was initially explored using bioinformatics methods. Furthermore, we conducted in vitro experiments to preliminarily validate the function of NEK2 in cervical cancer. RESULTS: NEK2 is overexpressed in almost all tumors, and mutation of NEK2 are associated with a poorer tumor prognosis. In addition, the correlation between NEK2 and immune features such as immune cell infiltration, immune checkpoint genes, tumor mutational burden (TMB), Microsatellite instability(MSI) etc. suggest that NEK2 could potentially be applied in the immunotherapy of tumors. CONCLUSION: NEK2 may be a potential pan-cancer biomarker and immunotherapeutic target for improving the efficacy of tumor therapy.